Organic Chemistry ReviewsChapter 11

Cindy Boulton

February 8, 2009

Alcohol vs Ethers Alcohol

CH3OH IUPAC: methanol Radiofuntional name: methyl alchol

Ether CH3OCH3

IUPAC: methoxymethane Radiofunctional name: dimethyl ether

Alcohol Chemistry and Properties Determined by –OH group -OH is a polar covalent bond Cable of hydrogen bond Raises boiling point Strong dipole Hydrogen has a pKa = 17

Readily removed by a strong base Dissolves polar and ionic compounds

Ether Chemistry and Properties Oxygen has a partial negative charge Two Carbons attached have a partial positive

charge Charges partially cancelled each other out Not as polar or reactive Used as a solvent

Inert: not as reactive

Synthesis of Alcohols Hydration of alkenes

By aqueous Sulfuric Acid (H+) Regiochemistry: Markovinkov, incoming hydrogen

goes to carbon with more hydrogen’s and forms a stable carbon cation

Stereochemistry: Racemic, an equal amount of new stereocenters (R and S) are formed

Pros: Sulfuric Acid is cheap Eliminate multiple steps (easy)

Cons: Primary R-OH is difficult to make Skeletal rearrangement is possible, carbocation will

rearrange to a higher order

Synthesis of Alcohols Oxymercuration/Demercuration

Alkene reacts with 1) Hg(OAc)2 2) NaBH4, OH-

Hg has multiple bonds and partial bonds with carbocation

Blocks alkanide migration/skeletal rearrangement Regiochemistry: Markovinkov Stereochemistry: Racemic Pros:

Skeletal rearrangement is blocked Cons:

Hg is toxic and expensive 2 Steps and multiple clean up steps Lower overall yield Primary Alcohols not likely formed

Synthesis of Alcohols Hydroboration-oxidation

Alkene reacts with 1) BH3 2) H2O2, OH-

Tranistion State: Boron and Hydrogen bonds to both Carbons, forms a trialkyl borane

Regiochemistry: Antimarkovinkov-incoming Hydrogen goes to Carbon with less Hydrogen, Sterics

Stereochemistry: Racemic, Syn addition

Pros: Can make Primary Alcohol No Skeletal rearrangement

Cons: 2 Steps Costly Needs clean up

Sulfonates Good leaving group for SN1, SN2, E1, and E2

reactions Stable ions and unreactive Resonance Structure Strong inductive effect

Alcohol is a bad leaving group but is changed to a have a sulfonate

Triflate (Tf): best Tosylate (Tf) Mesylate : worst

Conversion of Alcohols to Alkyl Halides Alcohol is a poor leaving group, but a halide is a

good leaving group for another reaction Conversion by HX (X = Cl, Br, I), PBr3, and SOCl2 1o Alcohol Mechanism

“SN2”- retains stereochemistry, no carbocation intermediate

3o Alcohol Mechanism “SN1”- sterics from the –R groups block SN2 reaction A stable carbocation intermediate is fromed Product is a racemic mixture with Optical Rotation = 0o

2o Alcohol Mechanism Either “SN1” or “SN2” depending on the –R groups Identified by optical rotation

Synthesis of Ethers Dehydration of alcohol

An alcohol reacts with H+ to protonate the –OH Second alcohol acts as a nucleophile and H2O acts

as a good leaving group Oxygen is protonated and removed by water of

something else forming symmetric or asymmetric ethers.

Reacts at an optimal temperature for the alcohol At different temperature can form an alkene

Synthesis of Ethers Williamson Synthesis

Alcohol reacts with a sulfonate and base to form a good leaving group The smaller of the two alcohols If the larger alcohol had been used, sterics would have

prevented the small nucleophile from attacking and an alkene would have been formed in an E2 reaction

A second alcohol reacts with a strong base to remove the proton on the hydroxyl forming an alkoxide, a good nucleophile The larger of the two alcohols

Control synthesis forming the ether using an SN2 reaction

Reaction of Ethers Cleaved by strong acids at high temperature

The ether becomes protonated by the acid forming an oxonium (O+)

The acid acts as a nucleophile attacking one of the Carbon groups

An acid and alcohol is formed A second acid reacts with the alcohol, protonating

the hydroxyl group The acid acts as a nucleophile reacting with the

carbon group Overall products: 2 alkyl halides and H2O

Epoxides Oxiranes or cyclooxapropanes Cyclic ether

2 Carbons and 1 Oxygen in a ring shape Strained and reactive

Synthesis of Epoxides Alkene reacts with a peroxy acid Oxygen connected to the –H reacts with the

alkene Forms enantiomers and racemic mixture

Epoxides Base Catalyzed Ring Opening

Hydroxyl attacks the carbon that is less crowded due to sterics

Oxygen remains bound to more crowded Carbon and is protonated

Forms a trans-alcohol due to anti addition Acid Catalyzed Ring Opening

Oxygen is protonated forming an oxonium Incoming H2O molecule attacks more substituted carbon

which forms a more stable carbocation due to electronics H2O molecule is deprotonated by a water molecule Forms a trans-alcohol due to anti addition

Give enantiomers of same original molecule Different from Syn Hydroxylation